MicroRNA-325-3p Facilitates Immune Escape of Mycobacterium tuberculosis through Targeting LNX1 via NEK6 Accumulation to Promote Anti-Apoptotic STAT3 Signaling
MicroRNA-325-3p Facilitates Immune Escape of Mycobacterium tuberculosis through Targeting LNX1 via NEK6 Accumulation to Promote Anti-Apoptotic STAT3 Signaling
复制标题
MicroRNA-325-3p 通过 NEK6 积累靶向 LNX1 促进抗凋亡 STAT3 信号传导，促进结核分枝杆菌的免疫逃逸
DOI：
10.1128/mbio.00557-20
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发表时间：
2020-05-01
期刊：
影响因子：
6.4
通讯作者：
Wu, Haibo
中科院分区：
文献类型：
--
作者：
Fu, Beibei;Xue, Weiwei;Wu, Haibo
结核分枝杆菌的细胞内存活导致细菌增殖和肺部感染的扩散，从而使结核病（TB）患者的病情恶化。本研究发现了M.通过调节宿主miR-325- 3 p表达，从而导致M.结核这些结果有助于进一步了解M.这些结果为耐药结核病的治疗提供了理论基础。摘要结核病是由结核分枝杆菌引起的一种危害人类健康的传染病。M.结核病通过逃避免疫监视和清除而在巨噬细胞中存活，这加剧了细菌增殖。然而，这种免疫逃逸的分子机制尚未完全了解。使用多个细胞和小鼠模型，我们发现microRNA-325- 3 p（miR-325- 3 p）在M.结核杆菌感染和Mir 325缺陷小鼠对M.结核我们证明了miR-325- 3 p直接靶向NEK 6的E3泛素连接酶LNX 1，并且这阻碍了NEK 6在巨噬细胞中的蛋白酶体降解。NEK 6的异常聚集导致STAT 3信号的激活，从而抑制凋亡过程，促进M.结核我们的发现不仅揭示了M.此外，它还可能为耐药结核病的治疗方法的发展提供新的见解。重要性结核分枝杆菌的细胞内存活导致细菌增殖和肺部感染的扩散，从而使结核病（TB）患者的病情恶化。本研究发现了M.通过调节宿主miR-325- 3 p表达，从而导致M.结核这些结果有助于进一步了解M.这些结果为耐药结核病的治疗提供了理论基础。
Intracellular survival of Mycobacterium tuberculosis results in bacterial proliferation and the spread of infection in lungs, consequently deteriorating the conditions of tuberculosis (TB) patients. This research discovers a new immune escape pathway of M. tuberculosis by modulating host miR-325-3p expression, thus leading to the intracellular survival of M. tuberculosis. These findings make a contribution to the understanding of the immune escape of M. tuberculosis, and they provide a theoretical basis for the development of therapeutic approaches for drug-resistant TB. ABSTRACT Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis that poses threats to the public. M. tuberculosis survives in macrophages by escaping from immune surveillance and clearance, which exacerbates the bacterial proliferation. However, the molecular mechanisms of this immune escape have not yet been fully understood. Using multiple cell and mouse models, we found that microRNA-325-3p (miR-325-3p) is upregulated after M. tuberculosis infection and Mir325-deficient mice show resistance to M. tuberculosis. We demonstrated that miR-325-3p directly targets LNX1, an E3 ubiquitin ligase of NEK6, and that this hampers the proteasomal degradation of NEK6 in macrophages. The abnormal accumulation of NEK6 leads to the activation of STAT3 signaling, thus inhibiting the process of apoptosis and promoting the intracellular survival of M. tuberculosis. Our findings not only reveal a new immune escape pathway of M. tuberculosis but also may provide new insights into the development of therapeutic approaches for drug-resistant TB. IMPORTANCE Intracellular survival of Mycobacterium tuberculosis results in bacterial proliferation and the spread of infection in lungs, consequently deteriorating the conditions of tuberculosis (TB) patients. This research discovers a new immune escape pathway of M. tuberculosis by modulating host miR-325-3p expression, thus leading to the intracellular survival of M. tuberculosis. These findings make a contribution to the understanding of the immune escape of M. tuberculosis, and they provide a theoretical basis for the development of therapeutic approaches for drug-resistant TB.